Pharmaceutical particulars : מידע רוקחי

6.    PHARMACEUTICAL PARTICULARS

6.1   List of excipients

α,α-Trehalose dehydrate
Sodium citrate dihydrate (for pH-adjustment)
Citric acid monohydrate (for pH-adjustment)
Polysorbate 80
6.2   Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.

6.3   Shelf life

The expiry date of the product is indicated on the packaging materials.
After reconstitution/dilution, from a microbiological point of view, the product should be used immediately. However, chemical and physical in-use stability has been demonstrated for 24 hours at 2°C-8°C.


6.4     Special precautions for storage

Store in a refrigerator (2 °C – 8 °C).

Do not freeze.
Keep the vial in the original carton in order to protect from light.

For storage conditions after reconstitution and dilution of the medicinal product, see section 6.3.

6.5     Nature and contents of container
Type I glass vial with a butyl rubber stopper and an aluminium/plastic flip-off seal, containing 50 mg powder.

Pack of 1 vial.

6.6     Special precautions for disposal and other handling
General precautions

Procedures for proper handling and disposal of anticancer medicinal products should be considered.

Proper aseptic technique throughout the handling of this medicinal product should be followed.
Instructions for reconstitution

Each single use vial must be reconstituted with 10.5 mL of water for injections to a final concentration of 5 mg/mL. Each vial contains a 10% overfill giving 55 mg of ADCETRIS per vial and a total reconstituted volume of 11 mL.

1. Direct the stream toward the wall of the vial and not directly at the cake or powder.
2. Gently swirl the vial to aid dissolution. DO NOT SHAKE.
3. The reconstituted solution in the vial is a clear to slightly opalescent, colourless solution with a final pH of 6.6.
4. The reconstituted solution should be inspected visually for any foreign particulate matter and/or discolouration. In the event of either being observed, discard the medicinal product.

Preparation of infusion solution

The appropriate amount of reconstituted ADCETRIS must be withdrawn from the vial(s) and added to an infusion bag containing sodium chloride 9 mg/mL (0.9%) solution for injection in order to achieve a final concentration of 0.4-1.2 mg/mL ADCETRIS. The recommended diluent volume is 150 mL.
The already reconstituted ADCETRIS can also be diluted into 5% dextrose for injection or Lactated Ringer's for injection.

Gently invert the bag to mix the solution containing ADCETRIS. DO NOT SHAKE.

Any portion left in the vial, after withdrawal of the volume to be diluted, must be disposed of in accordance with local requirements.

Do not add other medicinal products to the prepared ADCETRIS infusion solution or intravenous infusion set. The infusion line should be flushed following administration with sodium chloride 9 mg/mL (0.9%) solution for injection, 5% dextrose for injection, or Lactated Ringer's for injection.

Following dilution, infuse the ADCETRIS solution immediately at the recommended infusion rate.
Total storage time of the solution from reconstitution to infusion should not exceed 24 hours.

Determining dosage amount:
Calculation to determine the total ADCETRIS dose (mL) to be further diluted (see section 4.2): 
ADCETRIS dose (mg/kg) x patient’s body weight (kg)                   = Total ADCETRIS dose (mL) to be further diluted Reconstituted vial concentration (5 mg/mL)

Note: If patient’s weight is more than 100 kg, the dose calculation should use 100 kg. The maximal recommended dose is 180 mg.

Calculation to determine the total number of ADCETRIS vials needed:

Total ADCETRIS dose (mL) to be administered
= Number of ADCETRIS vials needed
Total volume per vial (10 mL/vial)

Table 20: Sample calculations for patients receiving the recommended dose of 1.8 mg/kg, 1.2 mg/kg or 0.9 mg/kg of ADCETRIS for weights ranging from 60 kg to 120 kga, b 
Recommended Patient Total dose =                                   Total volume to be           Number of vials dose        weight patient weight                                  dilutedc = total dose        needed = (kg)    multiplied by                                  divided by                   total volume to be recommended dose                               reconstituted vial           diluted divided by concentration                total volume per
(5 mg/mL)                    vial (10 mL/vial)
1.8 mg/kg (up           60 kg        108 mg                        21.6 mL                      2.16 vials to a maximum            80 kg        144 mg                        28.8 mL                      2.88 vials of 180 mg)              100 kg       180 mg                        36 mL                        3.6 vials 120 kgd      180 mg                        36 mL                        3.6 vials 1.2 mg/kg (up           60 kg        72 mg                         14.4 mL                      1.44 vials to a maximum            80 kg        96 mg                         19.2 mL                      1.92 vials of 120 mg)              100 kg       120 mg                        24 mL                        2.4 vials 120 kgd      120 mg                        24 mL                        2.4 vials 0.9 mg/kg (up           60 kg        54 mg                         10.8 mL                      1.08 vials to a maximum            80 kg        72 mg                         14.4 mL                      1.44 vials of 90 mg)               100 kg       90 mg                         18 mL                        1.8 vials 120 kgd      90 mg                         18 mL                        1.8 vials  a.     This table provides sample calculations for adult patients.
b.     For paediatric patients studied in clinical trials (6-17 years of age), body surface area-based dosing was calculated as 48 mg/m2 every two weeks in combination with AVD in a 28-day cycle or 72 mg/m2 every three weeks as monotherapy.
(See sections 5.1 and 5.2 for information on clinical studies conducted in paediatric patients.) c.     To be diluted in 150 mL of diluent and administered by intravenous infusion over 30 minutes.
d.     If patient’s weight is more than 100 kg, the dose calculation should use 100 kg.


Disposal

ADCETRIS is for single use only.
Any unused product or waste material should be disposed of in accordance with local requirements.